title: S100A14: novel modulator of terminal differentiation in esophageal cancer.
abstract: Aberrant keratinocyte differentiation is a key mechanism in the initiation of cancer. Because activities regulating differentiation exhibit altered or reduced capacity in esophageal cancer cells, it is vital to pinpoint those genes that control epidermal proliferation and terminal differentiation to better understand esophageal carcinogenesis. S100A14 is a member of the S100 calcium-binding protein family and has been suggested to be involved in cell proliferation, apoptosis, and invasion. The present study used immunohistochemistry analysis of S100A14 in clinical specimens of esophageal squamous cell carcinoma (ESCC) to show that decreased S100A14 is strongly correlated with poor differentiation. Furthermore, both mRNA and protein expression of S100A14 was drastically increased upon 12-O-tetra-decanoylphorbol-13-acetate (TPA) and calcium-induced esophageal cancer cell differentiation. Overexpression of S100A14 resulted in a G1-phase cell cycle arrest and promoted calcium-inhibited cell growth. Conversely, decreasing S100A14 expression significantly promoted G1-S transition and prevented the morphologic changes associated with calcium-induced cell differentiation. Molecular investigation demonstrated that S100A14 altered the calcium-induced expression of late markers of differentiation, with the most prominent effect on involucrin (IVL) and filaggrin (FLG). Finally, it was determined that S100A14 is transcriptionally regulated by JunB and that S100A14 and JunB status significantly correlated in ESCC tissue. In summary, these data demonstrate that S100A14 is transcriptionally regulated by JunB and involved in ESCC cell differentiation.
  
  
  CONCLUSIONS
  This study further differentiates the molecular mechanism controlling the development and progression of esophageal cancer.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China. liuzh@cicams.ac.cn.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.forename: Jianlin
authors.initials: J
authors.lastname: Ma
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sunkel
authors.forename: Aiping
authors.initials: A
authors.lastname: Luo
authors.forename: Fang
authors.initials: F
authors.lastname: Ding
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Huan
authors.initials: H
authors.lastname: He
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
authors.forename: Chengshan
authors.initials: C
authors.lastname: Xu
authors.forename: Qinge
authors.initials: Q
authors.lastname: Jin
authors.forename: Qianben
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
mesh_terms: D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D000091344:Filaggrin Proteins; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011498:Protein Precursors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; C581727:JunB protein, human; D011498:Protein Precursors; C462950:S100A14 protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C032253:involucrin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium